The recent and massive revival of green strategies to control plant diseases, mainly as a consequence of the Integrated Pest Management (IPM) rules issued in 2009 by the European Community and the increased consumer awareness of organic products, poses new challenges for human health and food security that need to be addressed in the near future. One of the most important green technologies is biocontrol. This approach is based on living organisms and how these biocontrol agents (BCAs) directly or indirectly interact as a community to control plant pathogens and pest. Although most BCAs have been isolated from plant microbiomes, they share some genomic features, virulence factors, and trans-kingdom infection abilities with human pathogenic microorganisms, thus, their potential impact on human health should be addressed. This evidence, in combination with the outbreaks of human infections associated with consumption of raw fruits and vegetables, opens new questions regarding the role of plants in the human pathogen infection cycle. Moreover, whether BCAs could alter the endophytic bacterial community, thereby leading to the development of new potential human pathogens, is still unclear. In this review, all these issues are debated, highlighting that the research on BCAs and their formulation should include these possible long-lasting consequences of their massive spread in the environment.